title: SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
abstract: The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development.
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan; CREST, Japan Science and Technology Agency, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan; PREST, Japan Science and Technology Agency, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan. Electronic address: isono@rcai.riken.jp.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Isono
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.forename: Manching
authors.initials: M
authors.lastname: Ku
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Rie
authors.initials: R
authors.lastname: Suzuki
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ishikura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Toyoda
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D063185:Epigenetic Repression; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C501292:Phc2 protein, mouse; D063146:Polycomb-Group Proteins; D063151:Polycomb Repressive Complex 2